A pilot study to increase the in vivo safety and infectivity of an in vitro expanded Plasmodium falciparum 3D7-MBE008 master cell bank in healthy subjects

This study will evaluate the in vivo safety and infectivity of a Plasmodium falciparum 3D7-MBE008 master cell bank (MCB) in healthy subjects using the induced blood stage malaria (IBSM) model. The study will be conducted in up to 2 subjects. The safety data review team (SDRT) will review the parasitaemia and safety data obtained from the first subject up until the end of Riamet® treatment before the second subject is inoculated with the malaria challenge agent. The malaria challenge agent, containing an estimated ~2,800 viable P. falciparum 3D7 parasite-infected RBCs in a volume of 2 mL, will be administered once intravenously on Day 0. The subject will undergo intravenous cannulation with an appropriate gauge cannula. The challenge agent will be injected immediately by an infectious disease physician, and the cannula again flushed with 5-10 mL of clinical grade saline. The cannula will then be removed, and haemostasis ensured by use of an appropriate dressing. The subject will be observed for a minimum of 60 minutes after inoculation. Subjects will be intravenously inoculated with P. falciparum-infected human erythrocytes on Day 0 (approximately 2,800 viable parasites). Subjects will be monitored daily via phone call or text message on Days 1 to 3 to solicit any adverse events (AEs). Subjects will then come to the clinical unit twice daily from Day 4, separated by approximately 12 hours, for safety assessments and to monitor the progression of parasitaemia by collecting blood samples and performing qPCR targeting the gene encoding P. falciparum 18S rRNA. Antimalarial treatment with artemether/lumefantrine (Riamet®) will be initiated when parasitaemia reaches =10,000 parasites/mL. Subjects will be admitted to the clinical unit for earlier treatment if: • they have a malaria clinical score greater than or equal to 6 • or if they experience an SAE, • or if they have a CTCAE grade 3 AE deemed possibly related to malaria and not self-resolved or relieved with concomitant medications, • or if the Principal Investigator (PI) or Co-Investigator (Co-I), both of whom are infectious diseases physicians, considers it necessary for subject safety. In this situation, the PI or Co-I will consult with the independent medical monitor; however, antimalarial medication may be administered prior to receiving approval if immediate treatment is deemed necessary for subject safety. Following initiation of treatment, subjects will be followed up as inpatients for at least 24 hours to ensure tolerance of the first three doses of Riamet® and adequate clinical response. Follow-up will then continue on an out-patient basis at 36, 48 and 72 hours post-treatment initiation for continued Riamet® dosing, safety monitoring, and to ensure clearance of parasitaemia. Additional visits may occur at the PI or Co-I’s discretion based on results of safety and parasitaemia assessments. Follow-up safety assessments will occur on Day 30±2 (phone call only), Day 60±2 (phone call only) and Day 90±2 (EOS). Primacin® (primaquine) may also be administered as a single oral dose if gametocytes are detected using qRT-PCR. The decision to administer primaquine will be made by the PI or Co-I in consultation with the independent medical monitor.